AKT1
Chr 14ADAKT serine/threonine kinase 1
Also known as: AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA
AKT1 encodes a serine/threonine protein kinase that regulates cellular metabolism, proliferation, survival, and growth through phosphorylation of downstream substrates in the PI3K/AKT signaling pathway. Mutations cause Proteus syndrome and Cowden syndrome 6, both presenting with excessive tissue growth and increased cancer risk, with inheritance following an autosomal dominant pattern. AKT1 is highly constrained against loss-of-function variants (pLI 0.98), consistent with its essential role in cellular homeostasis.
Limited evidence — not for standalone diagnostic reporting
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Highly missense-constrained (top ~0.1%)
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function, gain-of-function and dominant-negative). The Badonyi & Marsh model scores gain-of-function highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports loss-of-function (haploinsufficiency). Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
AKT1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Canadian Profiling and Targeted Agent Utilization Trial (CAPTUR)
RECRUITINGDabrafenib and Lapatinib in Treating Patients With Refractory Thyroid Cancer That Cannot Be Removed by Surgery
ACTIVE NOT RECRUITINGTesting the Addition of Ipatasertib to the Usual Chemotherapy Treatment (Paclitaxel and Carboplatin) for Stage III or IV Epithelial Ovarian Cancer
ACTIVE NOT RECRUITINGLevels of Circulating Tumor DNA as a Predictive Marker for Early Switch in Treatment for Patients With Metastatic (Stage IV) Breast Cancer
ACTIVE NOT RECRUITINGAdapting Treatment to the Tumor Molecular Alterations for Patients With Advanced Solid Tumors: MyOwnSpecificTreatment
RECRUITINGTrastuzumab Deruxtecan vs Endocrine Therapy in Low-HER2 HR+ Advanced Breast Cancer
RECRUITINGEvexomostat Plus PI3K or AKT Inhibitor and Fulvestrant in Patients With a PI3K Alteration and HR+/Her2- Breast Cancer
RECRUITINGSerial Circulating Tumor DNA (ctDNA) Monitoring During Adjuvant Capecitabine in Early Triple-negative Breast Cancer
RECRUITINGCapivasertib + CDK4/6i + Fulvestrant for Advanced/Metastatic HR+/HER2- Breast Cancer (CAPItello-292)
RECRUITINGA Phase 1 Study of ATV-1601 in Patients With Advanced Cancer That Have AKT1 E17K Mutations
ACTIVE NOT RECRUITINGInstitution of an Italian Registry and Biobank for Biological Sample Collection
RECRUITINGA Multicenter Phase III Clinical Study and Translational Research on Adaptive Neoadjuvant Therapy of De-escalation and Escalation for HER2-Positive Breast Cancer Based on Multi-Omics Response Evaluation Model
NOT YET RECRUITINGExternal Resources
Links to major genomics databases and tools